PFN3 (profilin 3) is an intron-less gene encoding an actin-binding protein that regulates cytoskeletal structure 1. As a testis-specific profilin isoform, PFN3 localizes to the acroplaxome-manchette complex and Golgi complex during spermiogenesis 23. PFN3 binds actin, poly-L-proline, and phosphoinositides (PtdIns(3)P, PtdIns(4,5)P2, PtdIns(4)P), but with distinct binding affinities compared to somatic profilin isoforms 3. PFN3 is essential for male fertility through its roles in acrosome biogenesis, manchette development, and proper mitochondrial organization 2. Loss of PFN3 causes subfertility with type II globozoospermia, characterized by abnormal sperm head morphology and reduced motility 2. PFN3 disruption impairs autophagy by dysregulating the AMPK/mTOR pathway and destabilizes the PFN3-ARPM1 complex 2. Beyond reproduction, PFN3 shows dysregulated transcriptional expression in gliomas, suggesting potential involvement in brain tumor malignancy 1. Additionally, genetic variants near the PFN3 locus (5q35.3) associate with nephrolithiasis susceptibility in genome-wide association studies 4. PFN3 also exhibits tissue-specific DNA methylation patterns useful for semen identification in forensic applications 56.